Previous studies from this laboratory and others have shown that both prolactin and estrogen stimulate growth of mammary tumors induced by dimethylbenzanthracene in the rat. This investigation aims to elucidate the mechanism of action and interaction of these two hormones. Experiments are designed to test the hypothesis that the stimulatory or inhibitory effects of hormones on tumor growth may be related to how they modulate the level of receptor sites of hormone-dependent tumors. Prolactin stimulating estrogen receptor binding capacities have been demonstrated both in in vivo and in vitro studies - progesterone, in contrast, inhibiting estrogen receptors. These studies have been confirmed recently by other investigators. Experiments are in progress to investigate the effect of estrogen upon prolactin receptors and also other hormones which influence tumor growth, upon estrogen and prolactin receptors, and also other hormones which influence tumor growth, upon estrogen and prolactin receptor sites. Furthermore, the pathway and molecular events of these stimulatory and inhibiting processes will be studied. Results from this investigation will provide information pertinent to hormonal therapy for human mammary carcinoma, and to a better understanding of the mechanisms of action and interaction of hormones. This may serve as a prototype for future investigations on the mechanisms of peptide-steroid interaction in other systems. BIBLIOGRAPHIC REFERENCES: Sasaki, G.H. and Leung, B.S.: On the mechanism of hormone action in 7,12-dimethylbenz(a)anthracene-induced mammary tumor. I. Prolactin and progesterone effects on estrogen receptor in vitro. Cancer 35:645-651, 1975. Leung, B.S., Sasaki, G.H. and Leung, J.S.: Estrogen-prolactin dependency in 7,12-dimethylbenz(a)anthracene-induced mammary tumor. Cancer Res. 35:621-627, 1975.